Ch 12 : Host defenses (Innate)

What are the 3 lines of host defense?

• First line

• Second Line

• Third line

Which lines of defense are innate?

• First and second line

Which line of defense is adaptive?

• Third line

How long does it take for each line of defense to kick in?

• First line = 0-4 hours

• Second line = 4-96 hours

• Third line = 96+ hours

Define first line of defense and list the different types of barriers

• Surface protection composed of anatomical and physiological barriers that keeps microbes from penetrating sterile body compartments

1. Physical barrier

2. Microbiota barrier

3. Chemical barrier

Define second line of defense and list the different methods

• Cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses

  • Goal is to eliminate/reduce as many microbes as possible, so the body can eventually fight the remaining microbes

1. Phagocytosis

2. Inflammation

3. Fever

4. Antimicrobial products

Define third line of defense and the types of cells involved

• Includes specific host defenses that must be developed uniquely for each microbe through the action of specialized WBCs

  • B & T cells

What line of defense do these characteristics align with?

• Any barrier that blocks invasion at the portal of entry

• Limits access to the internal tissues of the body

• Very general in action

First line of defense

What line of defense do these characteristics align with?

• Internalized system of protective cells and fluids

• Includes inflammation and phagocytosis

• Acts rapidly at both local and systemic levels once the first line of defense is breached

Second line of defense

What line of defense do these characteristics align with?

• Acquired as each foreign substance is encountered by lymphocytes

• Each different microbe produces unique protective response

• Provides long term immunity

Third line of defense

Which lines of defense are not affected by vaccinations?

• First and Second line

Which line of defense is affected by vaccines?

Third line

Which line of defense is innate (born with) and nonspecific (works the sam on any type of pathogen)?

First line

What are the types of physical barriers?

• Skin

• Mucous membranes

How does the skin act as a barrier? What can the skin do to remove microbes?

• It is the outermost layer of our body

• Tough layer that is impervious (nothing can easily pass through)

• Waterproof

Constant shedding of outer most layer of skin removes microbes

Where are mucous membranes located?

• Digestive tract

• Urinary tract

• Respiratory tract

• Eyes

How do mucous membranes act as barriers? Examples for eye, stomach, body?

• Mucous coating blocks entry and attachment of bacteria

• Blinking/tear production flush the eye’s surface

• Constant flow of saliva carries microbes to the harsh conditions of the stomach

• Vomiting and defecation evacuate harmful substances/organisms from the body

How do mucous membranes act as a barrier in the respiratory tract? Examples?

• Nasal hair traps larger particles like dust and dirt

• Copious flow of mucus + fluids provides flushing action

• Ex)

  • Sneeze reflex expels a large amount of air at high velocity

  • Foreign matter in the bronchi, trachea, and larynx triggers coughing to eject irritants

What is the ciliary escalator and how does it work? What kills cillia?

• Ciliated epithelium conveys trapped particles in mucus toward pharynx

  • Lining of respiratory tract

    • Always moving up, so it doesn’t let particles get to the lungs

• Chronic smoking

What are some ways chemical (physiological) barriers work?

• Sebaceous secretions exert an antimicrobial effect

• Specialized glands of the eyelids lubricate the conjunctiva with an antimicrobial secretion

• Lysozyme found in tears, saliva, and mucous hydrolyze the peptidoglycan in the cell wall of bacteria

• High lactic acid and electrolyte concentrations of sweat

• Acidic pH and fatty acid content of the skin

• Hydrochloric acid in the stomach, digestive juices and bile in the intestines

What are microbiological barriers (human microbiome) and how do they work?

• Forms a type of structural barrier

1. Can block the access of pathogens to epithelial surfaces/attachment site

   1. Our bodies normal microbiota already taking up those sites/surfaces

2. Creates competition for limited resources

   1. Microbes in our body are actively growing vs pathogens trying to grow

      1. Both need nutrients but microbes have the step 1 + larger number so they are most likely going to win

3. Creates an unfavorable environment for pathogens by altering the local pH

Crohn’s disease and ulcerative colitis may be the result of…

• Lack of healthy gut microbiome

  • If we lack certain microbes, it can predispose us to pathogens

• Ill trained gut

  • Can lead to tolerance 

    • Allergy to foods

For each of these barriers, state whether ts physical or chemical

• Hydrochloric acid of the stomach

• Sloughing of skin

• Lysozyme in saliva, tears, and mucous

• Ciliary escalator

• Peristalsis

• Chemical

• Physical

• Chemical

• Physical

• Physical

Is the second line of defense specific or nonspecific? What are the different methods?

Nonspecific

1. Phagocytosis

2. Inflammation

3. Fever

4. Antimicrobial proteins

What is phagocytosis? What does it do? What are the types of phagocytes?

• Cornerstone of inflammation

• Activity:

  • Actively searching tissue compartments and find microbes, particulate matter, and injured/dead cells

  • Ingest + eliminate these materials

  • Read immunogenic info (antigens)

    • Secrete cytokine which alerts body that pathogen is present

• Types:

  • Neutrophils

  • Monocytes

  • Macrophages

  • Dendritic Cells

Which phagocytes are present in blood?

• Neutrophils

• Monocytes

Which phagocytes are present in tissues?

• Macrophages

• Dendritic cells

What are neutrophils?

• Main goal is to kill pathogen - highly phagocytic

• First responder in inflammatory response to bacteria and other foreign materials and to damaged tissue

• It’s the highest WBC in blood (60-70%)

What phagocyte is the primary component of pus?

• Neutrophil

What does a high neutrophil count in the blood a common sign of?

Bacterial infection

What are macrophages?

• Highly phagocytic

• Some macrophages live in certain tissues and stay there during their life span

• Some macrophages are formed from monocytes that differentiate into macrophages after they move out of the bloodstream into the tissue

Kupffer cells are found in the…

Liver

Phagocytosis can be an ________ event or as part of ____________

• isolated, inflammation

What are the events of phagocytosis?

• Chemotaxis

• Adhesion

• Ingestion into phagosome

• Phagolysosome formation

• Destruction

• Excretion

What is chemotaxis in phagocytosis?

• Phagocyte moves into a region of inflammation with a deliberate sense of direction (GPS signal), they were attracted by a gradient of stimulant products from the parasite and host tissue at the site of injury

What are pathogen-associated molecular patterns (PAMPs)?

• molecules found on microbial surfaces recognized by phagocytes + other defensive cells

• Not present in mammals

• “Red flags” for phagocytes + other innate immunity cells

What are some types of bacterial PAMPs?

• Peptidoglycan

• Lipopolysaccharide (LPS)

What is a type of viral PAMP?

• double stranded RNA

What are Pattern recognition receptors? (PRRs)

• Found on immune cells and endothelial cells

• Recognize + bind to PAMPS

What is adhesion in phagocytosis?

• Phagocytes use their PRRs to recognize PAMPs on foreign targets, this receptor interaction causes phagocyte to attach to its target microbe

What is engulfment and phagosome formation in phagocytosis?

• Once phagocyte makes contact with its target and internalizes it in a vacuole called a phagosome, it will also secrete more cytokines to further amplify the innate response

• Phagosome:

  • Membrane bound structure

  • Contains the pathogen

    • Some pathogens have evolved & can escape this structure (Listeria)

What is phagosome formation and killing in phagocytosis?

• In a short time, lysosome fuses with phagosome to form a phagolysosome. Antimicrobial chemicals are released into this phagolysosome, which forms a toxic brew made to poison and dismantle the pathogen

• Lysosome:

  • Contains digestive machinery

• Phagolysosome:

  • Now contains engulfed pathogen + digestive machinery

What is destruction in phagocytosis?

• 2 separate systems of destructive chemicals await the microbes in the phagolysosome

1. Oxygen dependent system (respiratory burst/oxidative burst)

   1. Involves formation of several toxic derivatives of oxygen

      1. Superoxide, Hydrogen peroxide, Singlet oxide, Hydroxyl Ion

2. Enzymes

   1. DNase, RNase, Proteases, Lysozyme, Peroxidase

What is elimination in phagocytosis?

• Small bits of undigestile debris are released from the macrophage by exocytosis

How is inflammation identified? What are the causes for each?

• Rubor - redness

  • Caused by increased circulation + vasodilation in the injured area

• Calor - warmth

  • Caused by heat given off by the increased flow of blood

• Tumor - swelling/edema

  • Caused by fluid escaping into the tissues

• Dolor - pain

  • Caused by the stimulation of nerve endings

• Loss of function

  • Rare, not always present

Is the inflammatory response local or systemic?

Both

Factors that cause inflammation?

• Trauma from infection

• Tissue injury or necrosis due to physical/chemical agents

What are the main functions of inflammation?

1. Mobilize + attract immune components to site of injury

2. Destroy microbes + block their further invasion

3. Set in motion mechanisms to repair tissue damage + localize and clear away harmful substances

What is the immediate reacrion of inflammation?

• Release of chemical mediators and cytokines by the blood cells and tissue cells in the injured area

  • Some mediators are vasoactive, so they affect endothelial cells + smooth muscle cells of blood vessels

  • Some are chemotactic factors (chemokines) which affect WBCs

What releases cytokines?

• Macrophages

• Dendritic cells

• T/B cells

• Endothelial cells

Mast cells release?

Chemical mediators

• Ex) Histamine

If there is no pathogen present, and only mechanical damage what happens?

• Blood cells + tissues will release chemical mediators which call for inflammation

Steps of inflammation:

1. Vasodilation

2. Increased permeability

3. Diapedesis

4. Chemotaxis + Phagocytosis

5. Repair

Step 1 of inflammation, Vasodilation:

• Blood vessels in the vicinity will dilate

  • Increases blood flow into the target area

Step 2 of inflammation, Increase permeability:

• Endothelial cells in the walls of blood vessels contract and form gaps

  • Some blood components can leak out and these escaped fluids are called exudate

    • Neutrophils can now escape through these gaps

  • Accumulation of this exudate in the tissues causes edema

Step 3 of inflammation, Diapedsis:

• Migration of WBCs out of blood vessels into tissues

  • Neutrophils = first responders, macrophages will take over later

More neutrophil in inflammation =

Acute inflammaation

More monocytes/macrophages in inflammation =

Chronic inflammation

Step 4 of inflammation, Chemotaxis + Phagocytosis:

• Migration of cells in infected tissue in response to a specific chemical stimulus

Step 5 of inflammation, Repair:

• Repair damaged tissue

What are the benefits of edema and leaky blood vessels?

• Influx of fluid = dilute toxic substances

• Fibrin clot can trap microbes to prevent further spread

• Neutrophils aggregated at inflamed site are involved in phagocytosing + destroying bacteria, dead tissues, and particulate matter

What is pus?

• Accumulation of dead WBCs, liquified cellular debris, and bacteria

What is pyogenic?

• Bacteria such as streptococci, staphylococci, gonococci, and meningococci that stimulate formation of pus

What is fever in second line of defense

• Abnormally elevated body temp

• Can also be associated with certain allergies, cancers, and other illnesses

• If cause unknown = FUO

What is a nearly universal symptom of infection?

Fever

What is our body temperature maintained by? Around what temp C/F?

• Hypothalamus

• C = 37

• F = 98.6

What temps define a low grade fever?

• 37.7-38.3 C / 100-101 F

What temps define a high grade fever?

• 40.0-41.4 C / 104-106 F

What are pyrogens?

• Substances that reset the hypothalamic thermostat to a higher setting

  • Exogenous pyrogens: products of pathogens like viruses, bacteria, protozoa, fungi, endotoxin, blood/blood products, vaccines, injectable solutions from outside of body

  • Endogenous pyrogens: freed by monocytes, neutrophils, and macrophages during phagocytosis such as interleukin-1 (IL-1) and TNF

Benefits of fever?

• Inhibits multiplication of temp-sensitive microorganisms

• Speeds up hematopoiesis, phagocytosis, and specific immune reactions

Antimicrobial products: Interferon (IFN)

• Small proteins

• Produced naturally by certain WBC and tissue cells

  • Interferon gamma

  • Interferons alpha and beta - antiviral activity

Antimicrobial product: Complement

• Complement immune reactions

• Has over 30 blood proteins that work to destroy bacteria and certain viruses, parasites and nearby cells

• Needs to be activated before it can exert its effect

• Cascade reaction:

  • Sequential: first complement protein in chemical series activates the next complement which then activates the next and so on

Classical complement pathway =

Initiated by binding to the antibodies that are already bound to microbes

Alternatice complement pathway =

• Does not require antibody to get started

• Quicker than classical pathway

What are the protective functions of complement proteins?

1. Opsonization

   1. C3 protein is hydrolyzed into 2 fragments (C3b and C3a)

   2. C3b coats (opsonizes) the surface of a microbe which makes it an easier target for phagocytosis

2. Inflammation

   1. C3b protein cleaves the protein C5 into C5a and C5b

   2. C5b aids inflammation

3. MAC and lysis

   1. C5b fragment now free to form a complex with C6, C7, C8 and C9

   2. C9 called membrane attack complex (MAC)

      1. MAC positioned on + forms pores in the target cell’s membrane, causing it to lose structural integrity

         1. Leads to inappropriate flow of water + ions in and out of cells, and eventual lysis of the cell

Antimicrobial product: Antimicrobial peptides

• Short proteins of 12-50 amino acids

  • Defensin + others

• Able to insert themselves into bacterial membranes

• Can create pore in the membrane

  • If enough pores form, the cell lysis